LB‐PO‐01
Angiotensin II Receptor Blocker is Preferable to Calcium Channel Blocker to Improve Nocturnal Dipping Pattern in Untreated Hypertensives
Jin‐Man Cho, Hui‐Jeong Hwang, Eun‐Sun Jin, Chang‐Bum Park, Il‐Suk Sohn, Chong‐Jin Kim
Cardiovascular Center Kyung Hee University Hospital at Gangdong Republic of Korea
Nocturnal blood pressure (BP) decrease less than 10% is known as a nondipping BP pattern. Nondipping BP has been shown to be associated with target organ damage and poorer cardiovascular outcomes. It was suggested that the angiotensin II receptor blockers (ARBs) could improve nocturnal dipping by enhancing daytime sodium excretion. We elucidated the effects of ARBs and calcium channel blockers (CCBs) on 24‐hour ambulatory BP monitoring (ABPM) in untreated hypertensives.
Fifty patients with untreated hypertension (male:female =30:20; mean age 51 ± 14 years; the mean duration of medication 344 days) were examined by ABPM before and after antihypertensive medication. We divided those patients into two groups [CCB group treated with CCBs (male:female=9:11; mean age= 53 ± 15 years) and ARB group treated with ARBs (male:female=21:9; mean age=49 ± 13 years)]. The Δ dipping was defined to [nocturnal BP decrease (%) after medication] – [nocturnal BP decrease (%) before medication].
There were no significant differences in the clinical characteristics between two groups. The follow up nocturnal systolic and diastolic BP decrease were significantly smaller in CCB group than in ARB group (9.07 ± 10.16 vs. 14.33 ± 6.73, p=0.032 in systolic BP; 10.12 ± 9.77 vs. 16.54 ± 6.63, p=0.008 in diastolic BP). The Δ dipping was significantly smaller in CCB group than in ARB group (‐1.46 ± 7.44 vs. 4.13 ± 7.99, p=0.018 in systolic BP; ‐2.81 ± 7.78 vs. 5.11 ± 8.64, p=0.002 in diastolic BP).
In conclusion, ARBs can effectively improve nocturnal dipping in untreated hypertension.
Keywords
angiotensin receptor blocker; calcium channel blocker; blood pressure; dipping
LB‐PO‐02
Factors Influencing Screening for Hypertension in a Low Income Country
Fred Nuwaha, Geofrey Musinguzi
Makerere University School of Public Health Kampala Uganda
Background
Hypertension is common among adults but largely asymptomatic. A lot of people who have hypertension are un‐ware that they have the disease. Screening of adults for hypertension would increase awareness and it is recommended that all adults be screened for hypertension. There is need to understand factors influencing screening for hypertension with a view of suggesting remedial actions.
Methods
In a community based cross sectional survey people ≥ 15 years in Uganda were asked whether they have ever had their blood pressure measured. People then had their blood pressure, height and weight measured. They were also interviewed about their social‐demographic characteristics including smoking and consumption of alcohol. Independent predictors of having blood pressure ever measured were assessed using binary logistic regression.
Results
Of the 4539 people who were reached, 1267 (27.9%) had ever had their blood pressure measured. The independent predictors of having blood pressure measured were being female (AOR 4.15, CI 3.47‐4.97, P < 0.001) having attended school (AOR 1.52, CI 1.22‐1.89, P < 0.001) residing in an urban area (AOR 1.95, CI 1.69‐2.26, P < 0.001) having ever been married (AOR 2.44, 1.92‐3.12 P < 0.001) and being older than 25 years of age (AOR 2.33 CI, 1.93‐2.78 P < 0.001). Wealth status, physical activity, smoking, drinking of alcohol and body mass index did not predict screening for hypertension.
Conclusion
More than 70% of adults in this setting have never had their blood pressure measured. Measures are needed to enhance screening for hypertension.
Keywords
Hypertension; Cardiovascular Diseases; Sub‐saharan Africa; Awareness
LB‐PO‐03
Childhood Family Structure and Adult Hypertension Among African Americans: The Pitt County Study
Debbie S. Barrington1, Sherman A. James2
1National Institute on Minority Health and Health Disparities Bethesda MD United States2Duke University Durham NC United States
Objective
Childhood socioeconomic position has been found to have a long‐term influence on later‐life blood pressure. We examined whether other early‐life socio‐familial factors such as childhood family structure had an effect on hypertension among African American men and women.
Methods
To describe the independent associations between childhood family structure and adult hypertension, gender‐stratified multivariable logistic regression was performed utilizing data on 413 male and 758 female adult participants enrolled between 1988 and 2001 in the Pitt County Study, a community‐based prospective cohort study of African Americans in North Carolina. Hypertension was assessed at baseline in 1988, and childhood family structure was assessed in 2001 via Event History Calendar methodology. Covariates used for adjustment included measures of childhood socioeconomic position such as parental education, occupation and household deprivation, as well as adult socioeconomic position and health behaviors.
Results
African American men and women experienced similar childhood socio‐familial factors: 62% lived in a two‐parent household from birth to 13 years of age and 13% experienced a change in parental guardianship prior to 18 years of age. Prevalence of hypertension differed by gender, 32% for men and 25% for women. Men who resided in a two‐parent household during childhood had 26% lower odds of hypertension compared to those men who were not raised in a household with two adults, OR = 0.74, 95%CI: (0.64, 0.85); no association was found among women. Men who experienced a change in parental guardianship during childhood had 64% increased odds of hypertension compared to those men who never experienced a guardianship change, OR=1.64, 95%CI: (1.35, 2.00); no association was found among women.
Conclusion
The gender‐specific influence of these childhood social factors suggest that programs and policies designed to promote and maintain stable socio‐familial environments for all children may confer additional benefits of ameliorating morbidity and mortality from hypertension in African American men.
Keywords
African Americans; Hypertension; Family Characteristics; Social Conditions
LB‐PO‐04
Patients with Short Dipper Duration Have More Severe Diastolic Dysfunction
Chong‐Jin Kim, Jin‐Man Cho, Chang‐Bum Park, Eun‐Sun Jin, Byung‐Hyun Joe
Kyung Hee University Hospital at Gangdong Seoul Korea
Backgrounds
Hypertension is usually related to altered diastolic dysfunction and left ventricular hypertrophy (LVH). Diastolic dysfunction of LV considered as early hallmark of cardiac damage. Among the hypertensive patients, the non‐dippers tend to have more severe diastolic dysfunction and LVH than the dippers. And there was a report that the dipper duration is inversely correlated to target organ damage such as renal dysfunction. So, we hypothesized that dipper duration is related to cardiac damage in the dippers.
Method
We reviewed 24hour ambulatory blood pressure (ABP) monitorings of patients taken for a diagnosis of hypertension. We divided the patients into 2 groups, the dippers and the non‐dippers according to the 24hour ABP results and calculated the dipper duration during sleep in the dippers. We checked echocardiographic variables of diastolic dysfunction and left ventricular mass index (LVMI) as a marker of target organ damage.
Results
The total number of subjects enrolled this study was 152. Twenty two patients were classified to the non‐dippers and 130 patients to the dippers. As the non‐dippers were compared to the dippers, E/E' was higher in the non‐dippers (p=0.009). Among the dipper patients, we checked the relation between dipper duration and diastolic dysfunction. The dipper duration was inversely correlated to E/E'(r=‐0.195, p=0.026). The LVMI were correlated to dipper duration, but it was statistically not significant (r=‐0.154, p=0.08). The other echocardiographic variables showed no significant correlation related to dipper duration.
Conclusion
In the patients with high BP, the shorter dipper duration was related to the more frequent incidence of diastolic dysfunction.
Keywords
dipper; non‐dipper; ABP; diastolic
LB‐PO‐05
Genetic Influences on the Pharmaco‐kinetic and Pharmacodynamic Characteristics of Valsartan
Jin‐Man Cho, Chong‐Jin Kim, Byung‐Hyun Joe, Eun‐Sun Jin, Chang‐Bum Park
Kyung Hee University Hospital at Gangdong Seoul Korea
Background
Valsartan is an angiotensin II AT1 receptor blocker and is used for patient with hypertension. To investigate genetic factors affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of valsartan, single group, open label and pre‐ and post‐comparison clinical study was conducted.
Methods
Total 21 male Korean volunteers were enrolled. Each subject was administered placebo in first period and valsartan 80 mg (Diovan®) in second period. For PD analysis, 24‐hr blood pressure changes were monitored. For determination of valsartan in human plasma, rapid and sensitive high‐performance liquid chromatography‐ electrospray ionization tandem mass spectrometric method was used. For genetic analysis, we used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis. Patients were divided into two groups according to PK and PD parameters. PK parameters were Cmax, AUCt, AUCinf, and Tmax. Diurnal BP pattern change after medication was used as a PD parameter (drug responder vs. non‐responder). Whole genome genotyping data was processed by linear regression analysis for PK and PD parameters.
Results
Drug responders had greater drug absorption pattern than non‐responders. Functional locations of SNPs were mainly located on the flanking 5′UTR, intron and flanking 3′UTR. Significant SNPs in the PK and PD parameters were related to signaling pathways including calcium, MAPK and vascular smooth muscle contraction.
Conclusion
Several significant SNPs affect the ADME (absorption‐distribution‐metabolism‐excretion) and the PD differences of valsartan. Identified significant SNPs will help understanding of individual differences in responsiveness of valsartan.
Keywords
ARB; hypertension; phamacokinetic; pharmacodynamic
LB‐PO‐06
Predictors and Prevalence of Renal Damage in Japanese Patients with Primary Aldosteronism
Yoshitsugu Iwakura, Ryo Morimoto, Masataka Kudo, Yoshikiyo Ono, Masahiro Nezu, Sadayoshi Ito, Fumitosh Satoh
Tohoku University Hospital Sendai Japan
Higher prevalence of urinary albumin was reported in patients with primary aldosteronism than in those with essential hypertension. Although “glomerular hyperfiltration” was thought to be one of the mechanisms of albuminuria, this condition is considered to overestimate true renal function and mask real renal damage. This prospective study was designed to evaluate renal function during 12 months to identify the risk factors of decreasing glomerular filtration rate and prevalence of chronic kidney disease in primary aldosteronism. All patients diagnosed with primary aldosteronism were treated according to the results of adrenal venous sampling. 102 patients with aldosterone producing adenoma underwent adrenalectomy and 111 were treated with mineralocorticoid receptor antagonists. Blood pressure, urinary albumin excretion rate and estimated glomerular filtration rate were significantly reduced at 1 month after specific treatments as compared with values at first visit. Throughout the follow‐up period of twelve months, there were no significant increases of blood pressure or urinary albumin excretion, and no significant decreases of estimated glomerular filtration. Prevalence of chronic kidney disease increased after treatment. Multivariate regression analysis revealed that plasma aldosterone concentration and systolic blood pressure were strong independent predictors of albuminuria before intervention. In addition, urinary albumin excretion at the first visit was a predictor of decline of estimated glomerular filtration after treatment. Thus, we recommend earlier diagnosis and treatment of primary aldosteronism to prevent renal damage associated with higher levels of aldosterone.
Keywords
aldosterone; estimated GFR; urine albumin excretion; CKD
LB‐PO‐07
Antihypertensive Effects of Granulocyte Colony‐Stimulating Factor (GCSF) Not Involves Angiogenesis in Spontaneously Hypertensive Rats
Igor Oliveira Loss1, Thalles Ramos Almeida1, Eliângela Cobo1, Marilia Beatriz Cuba1, Carolina Salomão1, Vanessa Cappuano1, Nicola Montano3, Valdo José Dias Silva1
1Federal University of Triangulo Mineiro Uberaba MG Brazil2University of Milan Milan Lombardy Italy
The granulocytic colony stimulating factor (GCSF) is a hematopoietic growth factor with recognized beneficial effects in experimental models of ischemic cardiomyopathies, especially from its potential angiogenic and endothelium‐protector. We examined the effects of GCSF on microvascular rarefaction, endothelial function and hypertension in rats. During 14 days, adult female spontaneously hypertensive rats (SHR) were treated daily with Granulokine (100 μg/Kg), s.c. (SHR‐GCSF group) or saline (SHR‐CT group). Systolic blood pressure (SBP) and heart rate (HR) of the animals were monitored by tail plethysmography before and during the treatment (each 2 days). Then, the animals were anesthetized and catheterized for direct register of cardiovascular parameters. The blood pressure (BP) signal was recorded for 1 hour in freely‐moving conscious rats. To access the endothelial functions, were employed random doses of acetylcholine and sodium nitroprusside via a carotid artery on anesthetized rats. At the end, the animals were euthanized and heart, skeletal muscle (gastrocnemius) and kidney were removed, rinsed and fractioned to immunohistochemical (muscle's capillary density) and morphological (renal glomeruli) studies. The heart weights were measured before fractionation. The indirect measurements showed reduction of SBP levels (15‐20 mmHg) in GCSF‐treated group, compared to controls. Confirming this indication, the direct record of BP demonstrated lower levels of systolic, mean and diastolic BP in group SHR‐GCSF (respectively, 165±5, 141±5 and 118±6 mmHg, n = 12) that in group SHR‐CT (respectively, 187±5, 158±5 to 135±5 mmHg, n = 14, p <0.05). No diferences were observed in HR levels between both groups. Greater baroreflex sensitivity, better endothelial function, smaller cardiac hypertrophy and Bowman's space glomerular were observed in GCSF‐treated group. However, not were observed diferences capillary density between the groups. Chronic treatment (14 days) with GCSF promotes antihypertensive effects in SHR. The mechanism seem not involve angiogenic processes.
Keywords
hypertension; GCSF; SHR; endothelial function
LB‐OR‐08
Aliskiren Effect on Plaque Progression in Established Atherosclerosis Using High Resolution 3D MRI (ALPINE): A Double Blind Placebo Controlled Trial
Georgeta Mihai1, Juliet Varghese1, Liubov Gushchina1, Lisa Hafer1, Jeffrey A. Deiuliis1, Sanjay Rajagopalan†,1
1The Ohio State University Columbus OH United States2The Ohio State University Columbus OH United States
Background
The renin‐angiotensin system (RAS) is well recognized as a mediator of pathophysiologic events in atherosclerosis. We hypothesized that treatment with the renin inhibitor Aliskiren will prevent the progression of atherosclerosis as determined by the high‐resolution magnetic resonance imaging (MRI) measurements of arterial wall volume in the thoracic and abdominal aorta of high‐risk non‐diabetic patients with cardiovascular disease.
Methods and Results
This was a single center, randomized, double‐blinded, placebo‐controlled trial. After a 2‐week single‐blind placebo phase, patients were randomized to receive either placebo (n=37, age range: 64.5 ± 8.9 years) or 150 mg of Aliskiren (n=34, 63.9 ± 11.5). Treatment dose was escalated to 300 mg at 2 weeks, and maintained during the rest of the study. Patients underwent dark blood three dimensional (3D) MRI assessment of atherosclerotic plaque in the thoracic and abdominal segments at baseline and upon study completion/termination (up to 36 weeks of drug or matching placebo).
Results
Baseline sitting and central aortic blood pressures were 127 ± 13 mm Hg and 121 ± 11 in placebo and 125 ± 18 and 119 ± 17 mm Hg in Aliskiren, respectively with no change with Aliskiren treatment compared to placebo. Plasma renin concentration significantly increased in Aliskiren compared to placebo. Aliskiren resulted in significant progression of aortic wall volume [normalized total wall volume (TWV): 5.31 ± 6.57 mm3 vs. 0.15 ± 4.39 mm3, p=0.03, and percentage wall volume (PWV): 3.37±2.96 vs. 0.97±2.02%, p=0.04] compared to placebo. In an analysis of subjects on ACEI/ARB, atherosclerosis progression was observed only in the Aliskiren group but not in the placebo group.
Conclusions
Aliskiren use in patients with pre‐existing cardiovascular disease resulted in unexpected increase in atherosclerosis compared to placebo. These results may have implications for the use of renin inhibition as a therapeutic strategy in patients with cardiovascular disease especially in those on ACEI/ARB therapy.
Keywords
Renin; Atherosclerosis; Angiotensin II; Renin Inhibitors